The rulers of Chōshū were the descendants of the great Sengoku warlord Mōri Motonari. Motonari was able to extend his power over all of the Chūgoku region of Japan and occupied a territory worth 1,200,000 koku. After he died, his grandson and heir Mōri Terumoto became daimyō and implemented a strategy of alliance with Toyotomi Hideyoshi. This would later prove to be a great mistake. After Hideyoshi's death, the daimyō Tokugawa Ieyasu challenged the Toyotomi power and battled with Hideyoshi's trusted advisor Ishida Mitsunari at the Battle of Sekigahara. Mōri Terumoto was the most powerful ally of the Toyotomi and was elected by a council of Toyotomi loyalists to be the titulary head of the Toyotomi force. However the Toyotomi forces lost the battle due to several factors tied to Mōri Terumoto:
- His cousin Kikkawa Hiroie secretly made a deal with Tokugawa Ieyasu resulting in the inactivity of 15,000 Mōri soldiers during the battle.
- His adopted cousin Kobayakawa Hideaki and his 15,600 soldiers betrayed Ishida and joined the Tokugawa side.
- After assurances from Tokugawa Ieyasu, Terumoto gave up the formidable Osaka castle without a fight.
Despite its inactivity, the Mōri clan was removed from its ancestral home in Aki to Nagato Province (also known as Chōshū), and its holdings were drastically reduced from 1,200,000 to 369,000 koku.
This was seen as a great act of betrayal to the Mōri clan, and Chōshū later became a hotbed of anti-Tokugawa activities. The origins of this were evident in the tradition of the clan's New Year's meeting. Every year during the meeting, the elders and the administrators would ask the daimyo whether the time to overthrow the shogunate has come, to which the daimyo would reply: "Not yet, the shogunate is still too powerful."
This dream would eventually be realized some 260 years later, when the domain joined forces with the Satsuma Domain and sympathetic court nobles to overthrow the Tokugawa shogunate.
In 1865, the domain bought a war-ship Union from Glover and Co., an agency of Jardine Matheson established in Nagasaki, in the name of Satsuma Domain.
They led the fight against the armies of the former shōgun, which included the Ōuetsu Reppan Dōmei, Aizu, and the Ezo Republic, during the Boshin War. The domains' military forces of 1867 through 1869 also formed the foundation for the Imperial Japanese Army. Thanks to this alliance, Chōshū and Satsuma natives enjoyed political and societal prominence well into the Meiji and even Taishō eras.